There is a tremendous unmet need for cost-effective methods of synthesizing and screening large libraries of synthetic compounds. This project will develop a novel 'liquid array' directed synthesis platform, based on Encoded Sortable Particle (ESP) technology, to generate large, high quality libraries of pre-defined content. ESPs are optically-encoded microfabricated particles that can be manipulated using magnetic force. The overall aim of this project is to use ESP technology to develop a highly efficient combinatorial synthesizer that uses a directed sort strategy. Because our combinatorial synthesizer will allow the directed synthesis of any set of compounds, it will create libraries of defined content that can be screened more rapidly and at lower cost than comparable random libraries, while displaying compounds of higher purity, providing substantially more information, and delivering data of higher quality. The ESP-based libraries will provide a broad platform for many different kinds of assays. ESP-based libraries have the potential to be used in basic biomedical research, as well as high-throughput discovery and clinical diagnosis and prognosis of cancer, and a wide variety of other diseases.